1.Serum cytokine levels in patients with advanced non-small cell lung cancer: correlation with clinical outcome of erlotinib treatment.
Yong-sheng WANG ; Li-yun MIAO ; Lu LIU ; Hou-rong CAI ; Jing-jing DING ; Sheng-xiang REN ; Cai-cun ZHOU ; Gerald SCHMID-BINDERT
Chinese Medical Journal 2013;126(20):3931-3935
BACKGROUNDSerum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer (NSCLC) patients. This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC.
METHODSA total of 162 patients with advanced NSCLC who received erlotinib as either second or third line therapy were enrolled in this study. Blood samples were collected before the initiation of erlotinib treatment, and the levels of IL-1, IL- 2R, IL-6, and tumor necrosis factor (TNF)-α were assessed by enzyme-linked immunosorbent assay (ELISA). Cutoff points were defined as the median levels of IL-1 (low (≥26.5 pg/ml) and high (>26.5 pg/ml)), IL-2R (low ( = 115 pmol/L) and high (>15 pmol/L)), IL-6 (low (≤49.5 pg/ml) and high (>49.5 pg/ml)), and TNF-α (low (≤48.5 pg/ml) and high (>48.5 pg/ml)). Kaplan-Meier analysis was used to estimate the survival time, and Cox regression analyses were used to correlate cytokines and baseline clinical characteristics with clinical outcomes, including time to progression (TTP) and overall survival (OS).
RESULTSBetween January 2007 and May 2011, 162 patients were enrolled. Their median age was 58 years. In this group, 109 were males and 53 were females, 74 were former or current smokers and 88 were non-smokers. A total of 122 patients had adenocarcinoma, 27 had squamous cell carcinoma, and 13 had tumors with other types of histology. And 139 patients had an Eastern cooperative oncology group (ECOG) performance status of 0-1, while 23 scored at 2-3. Expression of IL-1, IL-2R, and IL-6 was not significantly associated with age, gender, ECOG performance status, smoking status, or histology and stage of tumor. Only TNF-α was associated with smoking status (P = 0.045). Survival analysis showed that patients with low levels of either IL-6 or TNF-α had a statistically longer TTP and OS than patients with high expression (P < 0.05). These cytokines remained significant upon multivariate analysis (P < 0.05).
CONCLUSIONIL-6 or TNF-α may serve as potential predictive biomarker for the efficacy of erlotinib.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; Cytokines ; blood ; Erlotinib Hydrochloride ; Female ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Protein Kinase Inhibitors ; therapeutic use ; Quinazolines ; therapeutic use
2.Clinical analysis and molecular genetic study of hereditary nonpolyposis colorectal cancer kindreds.
Ding-cun LUO ; Qi CAI ; Meng-hong SUN ; Yao-zhong NI ; Chong-wei TAO ; Zhe-jing CHEN ; Da-ren SHI
Chinese Journal of Surgery 2004;42(3):158-162
OBJECTIVETo study the clinicopathological and molecular genetic characteristics of hereditary nonpolyposis colorectal cancer (HNPCC), to enable the early diagnosis and to evaluate the treatment.
METHODSWe analyzed 12 families of HNPCC from Wenzhou, Zhejiang province, China. Mismatch repair genes hMSH2 and hMLH1 expression and microsatellite instability of tumor tissue were studied using microdissection, microsatellite analysis, immunohistochemical staining and Gene Scan analysis. Direct DNA sequencing of hMSH2 and hMLH1 were performed subsequently.
RESULTSAltogether 32 patients with colorectal cancer were recognized in 12 HNPCC families, with the median age of 45.2 years (75.0% before the age of 50 years). The proximal tumors accounted for 51.1%, while multiple colorectal cancers accounted for 34.4%. Poor differentiation cancers occupied half of the patients (53.1%). And 68.8% of the patients had the tumor of Dukes A and B. Among 12 HNPCC families, 7 cases in 6 HNPCC families developed extracolonic cancer. 13 cases died during follow up of 1 - 23 years. The median survival time was 6.4 years. 19 alive cases followed up from 1 to 28 years. All tumors (9/9) displayed microsatellite instability, with the half losing hMSH2 or hMLH1 expression. In the 5 genetic analyzed kindreds 3 possessed germline mutation. Two of three mutations have not been reported in the worldwide database previously.
CONCLUSIONHNPCC showed distinct clinicopathological characteristics. Microsatellite instability analysis and immunohistochemical staining might be the effective screening methods before direct DNA sequencing for the detection of mutation in mismatch repair genes. It is important to analyze the members of affected families.
Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Carrier Proteins ; China ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; metabolism ; pathology ; DNA Mutational Analysis ; DNA, Neoplasm ; chemistry ; genetics ; DNA-Binding Proteins ; analysis ; genetics ; Family Health ; Female ; Humans ; Immunohistochemistry ; Male ; Microsatellite Repeats ; genetics ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; Mutation ; Neoplasm Proteins ; analysis ; genetics ; Nuclear Proteins ; Proto-Oncogene Proteins ; analysis ; genetics
3.Time-dependent expression of astroglial S100beta following diffuse brain injury in rats.
Ping HUANG ; Yan-feng LIU ; Ya TUO ; Ping ZHANG ; Cun-jing DING ; Jie FANG ; Zheng-yuan WANG
Journal of Forensic Medicine 2006;22(1):4-6
OBJECTIVE:
To investigate the dynamics of the induction of S100beta in different parts of rat brain following the diffuse brain injury.
METHODS:
Immunohistochemistry and auto-image analysis were to determine the expression of astroglial S100beta after diffuse brain injury in rats. Forty rats were distributed into groups according to injury time of 30min, and2,4,12,24h, and 3,6 d after diffuse brain injury, and normal rats as control.
RESULTS:
The number of S100beta positive cells in the four areas increased significantly followed by a decrease, and then a further increase. The expression of S100beta could be detected increasing in 2h, and increased significantly in 4h, and it reached apex 12h after DBI, and decreased gradually to the level less than normal 3d, and returned to normal 7d following injury. In the postmortem injury groups, there were no significant changes in anti-S100beta immunoreactivities in four areas of brain compared to the control group.
CONCLUSION
The present study showed the time-dependent expression of S100beta is obvious following diffuse brain injury, and suggested S100beta be suitable as a marker for brain injury age determination.
Animals
;
Brain/pathology*
;
Brain Edema/pathology*
;
Brain Injuries/pathology*
;
Female
;
Immunohistochemistry
;
Male
;
Nerve Growth Factors/analysis*
;
Neuroglia/metabolism*
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
;
S100 Calcium Binding Protein beta Subunit
;
S100 Proteins/analysis*
;
Staining and Labeling
;
Time Factors
4.Antecolic versus retrocolic gastroenteric anastomosis for laparoscopic Roux-en-Y gastric bypass: a prospective randomized control trial.
Xian-ming LIU ; Cun-chuan WANG ; You-zhu HU ; Jing-ge YANG ; Jing HUANG ; Hui DING ; Jin-yi LI ; Yun-long PAN ; Ying-ying SHEN ; Chun-liang YU ; Hai-bo YU
Chinese Journal of Gastrointestinal Surgery 2011;14(6):422-424
OBJECTIVETo compare short-term postoperative outcomes between antecolic and retrocolic laparoscopic Roux-en-Y gastric bypass(LRYGB).
METHODSForty obesity patients were admitted into The First Affiliated Hospital of Jinan University from March 2008 to July 2010. All patients were randomly assigned to undergo antecolic (group A, 20 cases) and retrocolic (group B, 20 cases) gastroenteric anastomosis. Short-term outcomes were compared.
RESULTSLRYGB procedures were successfully performed in all the 40 patients. There were no significant differences between the two groups in estimated blood loss during surgery, time to flatus passage, time to resumption of oral intake, or length of postoperative hospital stay. The operation time was longer in group B than that in group A [(163.4±28.1) min vs.(131.8±22.7) min, P<0.05]. There were no patients developed internal hernia or anastomotic leakage in either group. Comparison of short-term gastrointestinal symptoms after surgery showed no statistical significance.
CONCLUSIONSAlthough retrocolic procedure may be closer to anatomical structure, antecolic and retrocolic anastomosis have comparable short-term outcomes after surgery. Further study is warranted to investigate long-term outcomes.
Adolescent ; Adult ; Female ; Gastric Bypass ; methods ; Gastroenterostomy ; methods ; Humans ; Laparoscopy ; Male ; Middle Aged ; Obesity, Morbid ; surgery ; Prospective Studies ; Treatment Outcome ; Young Adult
5.Diagnostic value of computed tomography (CT) histogram analysis in thyroid benign solitary coarse calcification nodules.
Le-Xing ZHANG ; Jing-Jing XIANG ; Pei-Ying WEI ; Jin-Wang DING ; Ding-Cun LUO ; Zhi-Yi PENG ; Zhi-Jiang HAN
Journal of Zhejiang University. Science. B 2018;19(3):211-217
This study was to investigate the diagnostic value of the computed tomography (CT) histogram in thyroid benign solitary coarse calcification nodules (BSCNs). A total of 89 thyroid solitary coarse calcification nodules (coarse calcification ≥5 mm, no definite soft tissue around calcification) confirmed either by surgery or histopathological examination in 86 cases enrolled from January 2009 to December 2015 were evaluated. These included 56 BSCNs and 33 malignant solitary coarse calcification nodules (MSCNs). Overall, 27 cut-off values were calculated by N (4≤N≤30) times of 50 Hounsfield units (HU) in the range of 200 to 1500 HU, and each cut-off value and the differences in the corresponding area percentages in the CT histogram were recorded for BSCN and MSCN. The optimal cut-off value and the corresponding area percentage were established by receiver operating characteristic (ROC) curve analysis. In the 19 groups with an ROC area under curve (AUC) of more than 0.7, at a cut-off value of 800 HU and at an area percentage of no more than 93.8%, the ROC AUC reached the maximum of 0.79, and the accuracy, sensitivity, and specificity were 75.3%, 80.4%, and 66.7%, respectively. At a cut-off value of 1050 HU and at an area percentage of no more than 93.6%, the accuracy, sensitivity, and specificity were 71.9%, 60.7%, and 90.9%, respectively. At a cut-off of 1150 HU and area of no more than 98.4%, the accuracy, sensitivity, and specificity were 70.8%, 57.1%, and 93.9%, respectively. At a cut-off of 600 HU and area of no more than 12.1%, the accuracy, sensitivity, and specificity were 61.8%, 39.3%, and 100.0%, respectively. Compared with the cut-off value of 800 HU and an area percentage of no more than 93.8%, the sensitivity of cut-off values and minimum areas of 1050 HU and 93.6%, of 1150 HU and 98.4%, and of 600 HU and 12.1%, was gradually decreasing; however, their specificity was gradually increasing. This can provide an important basis for reducing the misdiagnosis and unnecessary surgical trauma.
Adult
;
Calcinosis/diagnostic imaging*
;
Humans
;
Middle Aged
;
Thyroid Nodule/diagnostic imaging*
;
Tomography, X-Ray Computed/methods*
6. Synthesis of five types of nucleobase-alanines and their mechanisms of inhibiting proliferation of rat hepatoma cells RH35
Cun-Shuan XU ; Ya-Ping SONG ; Kai XU ; Hui YANG ; Yi DING ; Jing-Jing BI ; Qian-Yi ZHAO ; Ting XU
Acta Anatomica Sinica 2020;51(2):195-205
Objective Five types of nucleobase-alanines were synthesized to study their cytotoxicity and mechanism. Methods Five types of nucleobase-alanines were synthesized by the method of nucleophilic ring-opening of serine-lactone. MTT assay was used to detect their effects on the viability of rat normal hepatocytes BRL-3A and rat hepatoma cells RH35. Flow cytometry was used to detect their effects of cell cycle and apoptosis on BLR-3A and RH35. Real-time PCR was performed to detect their effects of proliferation/ apoptosis-related gene expression on these two cells. Results Five types of nucleobase-alanines were synthesized, including 1-uracil-L-alanine, 1-thymine-L-alanine, 1-cytosine-L-alanine, 9-adenine-L-alanine and 9-guanine-L-alanine. Among them, 1-cytosine-L-alanine and 9-guanine-L-alanine had significant lower half inhibition concentration(IC
7. Construction of aquaporin 9 gene knockout mice using CRISPR/Cas9 gene editing system
Quan-Cheng CHENG ; Jing FAN ; Huai-Cun LIU ; Hui-Ru DING ; Xuan FANG ; Jian-Wei WANG ; Chun-Hua CHEN ; Wei-Guang ZHANG
Acta Anatomica Sinica 2022;53(1):126-131
Objective To construct homozygous aquaporin 9(AQP-9)